Stathmokinetic Analysis of Granulosa Cell Proliferation in Antral Follicles of Cyclic Rats 1

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Abstract
On Day 1 of the estrous cycle (estrus), most of the largest follicles in the ovaries of rats appear to be healthy. By the following day, however, nearly 1/3 of all antral follicles show clear signs of atresia. The remaining healthy follicles are presumably those which will go on to ovulate. The object of this study was to distinguish between 2 possibilities: 1) that all of the largest follicles in the ovary on Day 1 subsequently undergo atresia on Day 2, and a new cohort of healthy follicles arises to replace them, or 2) that 1 single cohort of follicles on Day 1 is the source of both the healthy and atretic follicles seen on Day 2. The rate of granulosa cell proliferation was determined on each day of the 4-day estrous cycle using a metaphase arrest technique. Follicles grew most slowly on Day 4; small follicles (181-646 cells in the largest cross section) had a mitotic index (MI) of 8.1% after a 4-h block. In contrast, on Day 1 granulosa cells were proliferating rapidly; small follicles had an MI of 15.9%. This high rate of cell proliferation was also characteristic of large follicles. Estimated growth rates predict that, in healthy follicles, the number of granulosa cells should have almost doubled in the 24 h between Days 1 and 2. However, while the largest antral follicles in the ovaries on Day 1 had an average of 1064 cells in the largest cross section, the largest healthy follicles on Day 2 had only 1252 cells, rather than the expected 1763 cells. these healthy follicles must have had only 750 cells on Day 1, based on observed rates of cell proliferation. There was no indication that the rate of cell proliferation in healthy follicles fluctuated dramatically during the period between Days 1 and 2, or that the rate of growth of healthy follicles of similar size varied significantly within a single animal. All of the largest follicles in the ovary on Day 1 may become atretic the following day. The follicles which will go on to ovulate during the subsequent cycle appear to be derived from a cohort of smaller follicles. [The role FSH was also considered.].